This demonstration grant proposal is for a collaborative project involving the Department of Psychiatry and the Department of Medicine at FSKMC that proposes to undertake a comprehensive evaluation of buprenorphine, a novel opioid mixed agonist antagonist, in order to gain a better understanding of its efficacy as a potential pharmacological treatment for i.v. opioid drug abuse, Since i.v. drug abuse is one of the primary risk factors for exposure to HIV infection, andy new treatment that results in reduced i.v., drug abuse should lower the risks of infection and development of AIDs. Our proposed strategy is to conduct two concurrent sets of studies: 1) a series of small scale human laboratory studies that will better elucidate the pharmacology of buprenorphine and provide needed data for designing optimal treatment parameters and 2) a series of outpatient clinical trials that will examine the efficacy of buprenorphine treatment under naturalistic conditions and test a range of treatment parameters including those developed in laboratory studies. Human pharmacology studies will 1) characterize buprenorphine's opioid agonist dose-effects in relation to effects of methadone, with particular attention to differential shape of dose-effect functions at high doses, 2) characterize buprenorphine's antagonist dose-effects in relation to those of both methadone and naltrexone, 3) examine the interaction between methadone and buprenorphine in precipitation and substitution studies in order to develop procedures for transition from methadone to buprenorphine and 4) examine the interaction between buprenorphine and naltrexone in order to characterize efficacy of a combination product for drug abuse treatment. Treatment outcome studies will 1) compare clinical outcomes for buprenorphine versus methadone treatment in a short-term maintenance protocol, 2) evaluate buprenorphine dose-effect relationships during pharmacological treatment of i.v. drug abuse, 3) examine the effects of buprenorphine dosage tapering following several different treatment durations. 4) evaluate the clinical outcome associated with transition from methadone to buprenorphine and 5) evaluate the efficacy of treatment with a combination buprenorphine/naltrexone pharmacotherapy agent. Overall, this series of proposed studies should provide a comprehensive evaluation of buprenorphine's potential as a pharmacological adjunct in the treatment of intravenous opioid abusers as well as vital information about optimal treatment parameters.